CBHA Is a Family of Hybrid Polar Compounds That Inhibit Histone Deacetylase, and Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Endometrial and Ovarian Cancer CellsTakai N. · Ueda T. · Nishida M. · Nasu K. · Matsuda K. · Kusumoto M. · Narahara H.
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan
Objectives: We investigated the effect of a novel synthesized histone deacetylase inhibitor (HDACI), CBHA, on three endometrial cancer cell lines, two ovarian cancer cell lines, and normal human endometrial epithelial cells. Methods: Endometrial and ovarian cancer cells were treated with various concentrations of CBHA, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated. Results: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of CBHA, although normal endometrial epithelial cells were viable after treatment with the same doses of CBHA that induced growth inhibition in endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to CBHA decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Furthermore, CBHA treatment of these cell lines increased acetylation of H3 and H4 histone tails. Conclusions: These results raise the possibility that CBHA may prove particularly effective in the treatment of endometrial and ovarian cancers.
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